Exploring breast and prostate cancer RNA-seq derived radiosensitivity with the Genomic Adjusted Radiation Dose (GARD) model

Abstract

The use of a 10 gene transcriptional signature as part of the GARD model has been shown to be predictive of radiotherapy benefit for a range of cancers, with the potential to determine an optimal overall dose per patient. We used publicly available RNA-seq transcriptomics data from a luminal B breast cancer patient and from 14 prostate cancer patients to explore the radiosensitivity indices (RSI) and so GARD estimates of both tumour and proximal normal biopsies from each individual. Clear differences of clinical relevance in derived radiobiological properties between tumour and proximal normal tissues were evident for the breast cancer patient, whilst such differences across the prostate cancer cohort were more equivocal. Using the prostate cancer cohort’s median tumour predicted GARD value as a threshold for high therapeutic effect for radiotherapy, we found evidence that a higher overall prescribed dose than the widely used 72 Gy/36fx could benefit half of these patients. This exploratory study demonstrates the potential combining the GARD model with sequencing based transcriptomics could have in informing personalised radiotherapeutic practise for both breast and prostate cancer patients.

Keywords

• Radiation therapy
• Genomics
• Personalized medicine
• Prostate cancer
• Breast cancer
• GARD